The new prognostic score for unresectable or recurrent gastric cancer treated with nivolumab: A multi-institutional cohort study.

BACKGROUND: Real-world outcomes of nivolumab treatment for gastric cancer and associated prognostic factors remain unclear; the present study aimed to evaluate both items. METHODS: A total of 278 consecutive patients treated with nivolumab for gastric cancer during 2017-2019 were enrolled in this multi-institutional retrospective cohort study. The impact of laboratory findings, immune-related adverse events (irAEs), and clinicopathological factors on long-term survival was evaluated using the Cox proportional hazards model. RESULTS: The response rate was 11.7% in patients with measurable lesions. The overall and progression-free survival estimates were 6.77 and 2.53 months, respectively. The incidence of irAEs was 30.6% (6.8% for grade ≥3). There were no treatment-related deaths. Multivariate analysis revealed that C-reactive protein level of ≤0.5 mg/dL (hazard ratio = 0.476, P < .001), irAE occurrence (hazard ratio = 0.544, P < .001), albumin level of >3.5 g/dL (hazard ratio = 0.688, P = .045), performance status 0 (hazard ratio = 0.711, P = .028), lymphocyte count >1000/µL (hazard ratio = 0.686, P = .027), and differentiated histological type (hazard ratio = 0.740, P = .046) were independently associated with improved survival. The median survival of patients with four or more good prognostic factors was 18.3 months. CONCLUSION: Nivolumab showed safety and survival benefits in patients with previously treated unresectable or recurrent gastric cancer. Low C-reactive protein level, irAE occurrence, high albumin level, high lymphocyte count, and differentiated histological type may affect outcomes. The presence of four or more good prognostic factors may help identify likely long-term survivors.

High postoperative neutrophil-lymphocyte ratio and low preoperative lymphocyte-monocyte ratio predict poor prognosis in gastric cancer patients receiving gastrectomy with positive lavage cytology: a retrospective cohort study.

BACKGROUND: Long-term outcomes in gastric cancer patients with positive lavage cytology (CY1) are generally poor. This multi-institutional retrospective cohort study aims to evaluate the clinical significance of the neutrophil-lymphocyte ratio (NLR) and the lymphocyte-monocyte ratio (LMR) in CY1 gastric cancer patients. METHODS: A total of 121 CY1 gastric cancer patients without other non-curative factors, who underwent macroscopically curative resection, were enrolled in this study. The cutoff values of preoperative NLR (pre-NLR), postoperative NLR (post-NLR), preoperative LMR (pre-LMR), and postoperative LMR (post-LMR) were defined by the Contal and O'Quigley method as 2.3, 3.0, 2.5, and 3.2, respectively. A Cox proportional hazard model was used to identify the independent prognostic factors among NLR, LMR, and other clinicopathological factors. RESULTS: There were significant differences in the overall survival (OS) between the two groups: high post-NLR groups vs. low post-NLR group (median survival time, months) (10.9 vs. 22.8, P = 0.006) and high pre-LMR group vs. low pre-LMR group (21.3 vs. 11.0, P = 0.001). The LMR value elevated significantly after gastrectomy (P = 0.020), although not in the NLR value (P = 0.733). On multivariate analysis, high post-NLR (hazard ratio = 1.506; 95% confidence interval = 1.047-2.167; P = 0.027), low pre-LMR (1.773; 1.135-2.769, 0.012), and no postoperative chemotherapy (1.558; 1.053-2.305, 0.027) were found to be independent prognostic factors for adverse OS. CONCLUSIONS: Because a combination of high post-NLR and low pre-LMR may be an adverse prognostic marker in resectable CY1 gastric cancer patients, it is necessary to conduct a prospective trial to confirm a useful perioperative chemotherapeutic regimen for these patients.

Real-World Therapeutic Outcomes of S-1 Adjuvant Chemotherapy for pStage II/III Gastric Cancer in the Elderly.

BACKGROUND: The predictive factors for discontinuation of S-1 administration and prognostic factors in elderly patients with pStage II/III gastric cancer receiving S-1 adjuvant chemotherapy remain unclear. METHODS: Between January 2004 and December 2016, 80 elderly gastric cancer patients (≥70 years) undergoing curative D2 gastrectomy were enrolled in this study. Predictive factors for completion of S-1 administration over 1 year, adverse events due to S-1 administration, and prognostic factors for overall survival (OS) and relapse-free survival (RFS) were evaluated. RESULTS: Twenty-eight patients (35%) completed 8 courses of S-1. The median relative dose intensity was 82.1% (IQR 31.1-100%). The incidence rates of hematological and nonhematological adverse events were acceptable. Distal gastrectomy was an independent predictive factor for completion of S-1 administration (odds ratio [OR] 0.364; 95% confidence interval [CI] 0.141-0.939; p = 0.037). Higher postoperative neutrophil count/lymphocyte count (N/L) ratio and more advanced stage adversely influenced OS. Multivariate analysis revealed that a higher postoperative N/L ratio and more advanced stage adversely affected RFS. CONCLUSION: To complete adjuvant S-1 administration to elderly patients with pStage II/III gastric cancer, total gastrectomy should be avoided if possible. A new regimen for elderly gastric cancer patients with higher postoperative N/L ratios and more advanced stage should be established.

Vasculature-driven stem cell population coordinates tissue scaling in dynamic organs.

Stem cell (SC) proliferation and differentiation organize tissue homeostasis. However, how SCs regulate coordinate tissue scaling in dynamic organs remain unknown. Here, we delineate SC regulations in dynamic skin. We found that interfollicular epidermal SCs (IFESCs) shape basal epidermal proliferating clusters (EPCs) in expanding abdominal epidermis of pregnant mice and proliferating plantar epidermis. EPCs consist of IFESC-derived Tbx3+-basal cells (Tbx3+-BCs) and their neighboring cells where Adam8-extracellular signal-regulated kinase signaling is activated. Clonal lineage tracing revealed that Tbx3+-BC clones emerge in the abdominal epidermis during pregnancy, followed by differentiation after parturition. In the plantar epidermis, Tbx3+-BCs are sustained as long-lived SCs to maintain EPCs invariably. We showed that Tbx3+-BCs are vasculature-dependent IFESCs and identified mechanical stretch as an external cue for the vasculature-driven EPC formation. Our results uncover vasculature-mediated IFESC regulations, which explain how the epidermis adjusts its size in orchestration with dermal constituents in dynamic skin.

Comparison of Converse Ω Anastomosis and Extracorporeal Anastomosis After Laparoscopic Distal Gastrectomy for Gastric Cancer.

BACKGROUND: Converse Ω anastomosis is a recently developed technique of delta-shaped anastomosis for intracorporeal gastroduodenostomy to simplify the anastomotic procedures and reduce their potential risks. This study aimed to evaluate the safety and effectiveness of converse Ω anastomosis, comparing it with conventional extracorporeal Billroth-I anastomosis after laparoscopic distal gastrectomy (LDG) for gastric cancer. PATIENTS AND METHODS: Among 169 gastric cancer patients who underwent LDG with Billroth-I anastomosis anastomosis between April 2013 and March 2018, we selected 100 patients by propensity score matching (50 in the converse Ω anastomosis group and 50 in the extracorporeal anastomosis group). Patients' characteristics, intraoperative outcomes, postoperative complications, and survival time were compared between the 2 groups. RESULTS: Median anastomosis time was significantly longer in the converse Ω group than in the extracorporeal group (40.0 vs. 30.5 min, P=0.005). However, the total procedure time did not differ significantly between the groups. Intraoperative blood loss volume was significantly lower in the converse Ω group than in the extracorporeal anastomosis group (40 vs. 120 mL, P<0.001). There were no significant differences in the number of dissected lymph nodes, postoperative morbidity, mortality, or length of hospital stay. The postoperative body mass index and the prognostic nutritional index did not differ between the groups 1 year after surgery. There were no significant differences in overall survival and relapse-free survival between the 2 groups. CONCLUSIONS: Converse Ω anastomosis is feasible and safe. This novel technique can be adopted as a treatment option for reconstruction after LDG in patients with early-stage gastric cancer. Therefore, the risks and benefits of converse Ω anastomosis after LDG should be confirmed in larger cohorts.

Prognostic Impact of the Neutrophil-to-Lymphocyte Ratio in Borderline Resectable Pancreatic Ductal Adenocarcinoma Treated with Neoadjuvant Chemoradiotherapy Followed by Surgical Resection.

BACKGROUND: Increasing evidence suggests that cancer-associated inflammation, as indicated by markers such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and modified Glasgow Prognostic Score (mGPS), predicts poor outcomes in pancreatic cancer. In this study, the associations between systemic inflammation markers and survival were examined in borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) patients who underwent neoadjuvant chemoradiotherapy (NACRT) followed by surgical resection. METHODS: From April 2009 to December 2017, 119 patients diagnosed with BR-PDAC and receiving NACRT followed by radical surgery were included in this retrospective study. The associations between the pre- and post-NACRT NLR, PLR, mGPS, and clinicopathological characteristics, as well as their predictive values for survival outcomes, were analyzed. This study was approved by an institutional review board at Yokohama City University (B180600049). RESULTS: On multivariate analysis with a Cox's proportional hazards regression model, post-NACRT NLR ≥3 (p = 0.040; hazard ratio, 2.24; 95% CI 1.28-3.91) and lymph node metastasis (p = 0.002; hazard ratio, 2.33; 95% CI 1.36-3.99) were significantly associated with shorter overall survival. The median survival time was 22.0 months for patients with post-NACRT NLR ≥3 and 45.0 months for patients with post-NACRT NLR <3 (p = 0.028). CONCLUSIONS: The NLR following NACRT might predict survival in BR-PDAC patients. Patients with an elevated post-NACRT NLR or positive lymph node metastasis may be candidates for stronger adjuvant therapies.

MiR-194-5p in Pancreatic Ductal Adenocarcinoma Peritoneal Washings is Associated with Peritoneal Recurrence and Overall Survival in Peritoneal Cytology-Negative Patients.

BACKGROUND: Peritoneal dissemination is one of the major recurrence patterns in patients with pancreatic ductal adenocarcinoma (PDAC) and is associated with poor prognosis. Here, we assessed the diagnostic potential of microRNA (miRNA) profiles in peritoneal washings for prediction of peritoneal dissemination in PDAC. PATIENTS AND METHODS: From January 2016 to July 2017, peritoneal washings were obtained prospectively from 59 patients with PDAC undergoing surgery the Yokohama City University Hospital. MiRNA expression was evaluated by Agilent human miRNA microarray and quantitative reverse-transcription polymerase chain reaction. RESULTS: Microarray analysis identified upregulated and downregulated miRNAs in peritoneal washings of patients with peritoneal dissemination. We validated four miRNAs (miR-141-3p, miR-194-3p, miR-194-5p, and miR-200c-3p) with high expression in peritoneal washings. The cumulative incidence rate of peritoneal recurrence in peritoneal cytology-negative patients in the miR-194-5p high group was significantly higher than that in the miR-194-5p low group (p = 0.002). Univariate and multivariate analyses revealed that high miR-194-5p was associated with overall survival (OS). CONCLUSIONS: High expression of miR-194-5p in peritoneal washings is associated with peritoneal recurrence and poor OS in patients with peritoneal cytology-negative PDAC.

Isolated breast metastasis from gastric cancer in a male patient.

A 72-year-old man underwent total gastrectomy for gastric cancer (por2, T3, N2, Stage IIIA). Eleven courses of postoperative chemotherapy with TS-1 (tegafur/gimeracil/oteracil) were administered. Five months after surgery, the serum carcinoembryonic antigen value was slightly elevated. However, computed tomography did not reveal any metastatic lesions in other organs. Two years after surgery, the patient felt a mass in the left mammary. A 2-cm tumor was palpable in the central portion of the breast. Ultrasonography revealed a hypoechoic tumor, which was Class 3 on aspiration biopsy cytological examination. No mass was detected on positron emission tomography-computed tomography. The mammary gland tumor increased in size to 3 cm, and a core needle biopsy procedure was performed. Histological examination findings revealed breast metastasis of gastric cancer. No other recurrence was found, and radical mastectomy was performed 2 years and 5 months after gastrectomy. Immunohistological analysis of the resected material confirmed breast metastasis of the gastric cancer. Two courses of TS-1 + cisplatin were administered, but this treatment was subsequently terminated because the patient experienced Grade 3 diarrhea and neutropenia. Three years and 1 month after the gastrectomy, the tumor recurred in the pelvic area. Chemotherapy and radiation therapy were performed, but the patient's overall condition became progressively worse, and he died 3 years and 9 months after gastrectomy.

Tbx3-dependent amplifying stem cell progeny drives interfollicular epidermal expansion during pregnancy and regeneration.

The skin surface area varies flexibly in response to body shape changes. Skin homeostasis is maintained by stem cells residing in the basal layer of the interfollicular epidermis. However, how the interfollicular epidermal stem cells response to physiological body shape changes remains elusive. Here, we identify a highly proliferative interfollicular epidermal basal cell population in the rapidly expanding abdominal skin of pregnant mice. These cells express Tbx3 that is necessary for their propagation to drive skin expansion. The Tbx3+ basal cells are generated from Axin2+ interfollicular epidermal stem cells through planar-oriented asymmetric or symmetric cell divisions, and express transit-amplifying cell marker CD71. This biased division of Axin2+ interfollicular epidermal stem cells is induced by Sfrp1 and Igfbp2 proteins secreted from dermal cells. The Tbx3+ basal cells promote wound repair, which is enhanced by Sfrp1 and Igfbp2. This study elucidates the interfollicular epidermal stem cell/progeny organisation during pregnancy and suggests its application in regenerative medicine.The abdominal skin expands rapidly during pregnancy. Here the authors show that a population of highly proliferative stem cell progenies expressing the transcription factor Tbx3 is required for abdominal skin expansion in pregnant mice.

Clinical characteristics of patients with diabetes mellitus and fatty liver diagnosed by liver/spleen Hounsfield units on CT scan.

Objective The leading cause of liver injuries in diabetes mellitus may be associated with fatty liver. We aimed to elucidate the relationship between fatty liver and diabetes characteristics. Methods Retrospectively, 970 patients with diabetes were analysed. Fatty liver was diagnosed when the liver/spleen Hounsfield unit ratio by computed tomography was below 0.9. Clinical diabetes characteristics were compared between patients with and without fatty liver. Results Of 970 patients (717 male and 253 female; mean age 64.4 years), 175 males (24.4%) and 60 females (23.7%) had fatty liver. None of the 28 patients with type 1 diabetes had fatty liver. In male patients with type 2 diabetes, age, visceral adipose tissue (VAT), albumin, alanine amino-transferase (ALT), and triglycerides were independently associated with fatty liver. In females, age and bilirubin were associated with fatty liver. Conclusions Fatty liver is associated with type 2 diabetes characteristics, including younger age and elevated VAT, albumin, ALT, and triglycerides in males and younger age and elevated bilirubin levels in females.

BNIP3 upregulation via stimulation of ERK and JNK activity is required for the protection of keratinocytes from UVB-induced apoptosis.

The human skin has an important role in barrier function. Ultraviolet rays (UV) from sunlight exposure can cause cell apoptosis in the skin epidermis, resulting in the disruption of the barrier. Previously, we have demonstrated that BNIP3 stimulates autophagy in epidermal keratinocytes and has a protective effect in these cells upon UVB irradiation. In this study, we found that the accumulation of reactive oxygen species (ROS) by UVB irradiation was sufficient to trigger the activation of JNK and ERK mitogen-activated protein kinase (MAPK) in human primary epidermal keratinocytes. In turn, activated JNK and ERK MAPK mediated the upregulation of BNIP3 expression. Treatment with an antioxidant reagent or a specific inhibitor of MAPK, U0126, and a JNK inhibitor significantly attenuated the expression of BNIP3 triggered by UVB, followed by the induction of cell death by apoptosis. Furthermore, UVB-induced apoptosis was significantly stimulated by chloroquine or bafilomycin A1, an inhibitor of autophagy. Moreover, BNIP3 was required for the degradation of dysfunctional mitochondria upon UVB irradiation. These data clearly indicated that BNIP3-induced autophagy, which occurs via UVB-generated ROS-mediated JNK and ERK MAPK activation, has a crucial role in the protection of the skin epidermis against UVB irradiation.

Essential roles of Tbx3 in embryonic skin development during epidermal stratification.

Stepwise differentiation of epidermal cells is essential for development of stratified epithelium, but the underlying mechanisms remain unclear. Here, we show that Tbx3, a member of the T-box family of transcription factors, plays a pivotal role in this mechanism. Tbx3 is expressed in both basal and suprabasal cells in the interfollicular epidermis of mouse embryos. Epidermis-specific Tbx3 conditional knockout (cKO) embryos are small in size and display a thinner epidermis with an impaired barrier function. In the Tbx3 cKO epidermis, keratin 5-positive undifferentiated cells, which reside in both basal and suprabasal layers of wild-type embryos, are localized exclusively in the basal layer. In addition, mRNA expression levels of granular cell markers are increased in the Tbx3 cKO epidermis, suggesting that Tbx3 prevents premature differentiation of spinous cells. We further show that Tbx3 maintains the proliferative potential of basal cells and ensures their planar-oriented cell division. Moreover, Tbx3 is shown to be required for the expression of Hes1, a well-known Notch signaling target protein that is essential for epidermal development. We therefore propose that Tbx3 functions upstream of Hes1 to regulate proliferation and differentiation of basal and suprabasal cells during epidermal development.

Beneficial Effects of the Genus Aloe on Wound Healing, Cell Proliferation, and Differentiation of Epidermal Keratinocytes.

Aloe has been used as a folk medicine because it has several important therapeutic properties. These include wound and burn healing, and Aloe is now used in a variety of commercially available topical medications for wound healing and skin care. However, its effects on epidermal keratinocytes remain largely unclear. Our data indicated that both Aloe vera gel (AVG) and Cape aloe extract (CAE) significantly improved wound healing in human primary epidermal keratinocytes (HPEKs) and a human skin equivalent model. In addition, flow cytometry analysis revealed that cell surface expressions of ß1-, α6-, ß4-integrin, and E-cadherin increased in HPEKs treated with AVG and CAE. These increases may contribute to cell migration and wound healing. Treatment with Aloe also resulted in significant changes in cell-cycle progression and in increases in cell number. Aloe increased gene expression of differentiation markers in HPEKs, suggesting roles for AVG and CAE in the improvement of keratinocyte function. Furthermore, human skin epidermal equivalents developed from HPEKs with medium containing Aloe were thicker than control equivalents, indicating the effectiveness of Aloe on enhancing epidermal development. Based on these results, both AVG and CAE have benefits in wound healing and in treatment of rough skin.

[Pathological complete response in 2 patients with cT4 esophageal cancer treated with neoadjuvant chemoradiation therapy].

We report the cases of 2 patients with clinical T4( cT4) esophageal cancer who achieved pathological complete response on treatment with neoadjuvant chemoradiation therapy. Case 1 involved a 68-year-old woman who was diagnosed as having cT4 advanced esophageal cancer( with involvement of the aorta and left pulmonary vein). Neoadjuvant chemoradiation therapy with 5-fluorouraci(l 5-FU)( 800 mg/m2, days 1-5 and days 29-33), cisplatin( CDDP 80 mg/m2, days 1 and 29), and radiation (39.6 Gy/22 Fr) was administered, and the tumor showed a partial response (PR). Case 2 involved a 69-year-old man who was diagnosed as having cT4 advanced esophageal cancer( with involvement of the main bronchus). Neoadjuvant chemoradiation therapy with 5-FU( 800 mg/m2, days 1-5 and days 29-33), CDDP( 80 mg/m2, days 1 and 29), and radiation( 39.6 Gy/22 Fr) was administered, and the tumor showed a clinical PR. After tumor response was noted, curative esophagectomy was performed in both cases, without any complications, and a pathological complete response was achieved in both patients.

Comparison of the Asthma Health Questionnaire-33-Japan and the short-form 36-item health survey for measuring quality of life in Japanese patients with asthma.

BACKGROUND: The Asthma Health Questionnaire (AHQ)-Japan is useful for assessing quality of life (QOL) in Japanese patients with asthma. However, no studies have compared the AHQ-Japan to other QOL instruments. METHODS: The AHQ-33-Japan and the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36) were completed simultaneously by 126 Japanese patients with asthma (48 men, 78 women; 58.1 +/- 17.3 years of age), and the data were compared. RESULTS: Poor negative correlations (correlation coefficient (r) = -0.20 to -0.44, P < 0.05) were observed for 38 combinations of the subscales of these QOL instruments. As the severity of the patients' asthma increased, the scores of most subscales of both QOL instruments became worse. However, the AHQ-33 was more sensitive for severity than the SF-36. On logistic regression analysis, high Asthmatic Symptoms, Factors which Worsened Symptoms, Emotion, Daily Activity, and Social Activity subscale scores, as well as a high total 32-item score, of the AHQ-33 were associated with an increased risk of moderate to severe asthma. On the other hand, only the Physical functioning subscale score of the SF-36 was associated with an increased risk of moderate to severe asthma. CONCLUSIONS: Our results show that the AHQ-33 is useful as a disease-specific QOL instrument in Japanese patients with asthma and that it is better than the SF-36, which is a generic QOL instrument. In the future, the AHQ-33 should be compared to other asthma-specific questionnaires.

Effects of dietary supplements on the Fischer ratio before and after pulmonary rehabilitation.

Recently, efforts in comprehensive pulmonary rehabilitation for COPD have been made, including education, physical therapy, occupational therapy, nutrition, nursing, medication and counseling. Each patient focuses on a different element. Supplying adequate nutrition, among others, is essential for comprehensive pulmonary rehabilitation, as well as survival. In this study, the utility of efficient nutritional supplement therapy before and after pulmonary physical therapy was investigated by adding an amino acid drink with a high Fisher ratio to comprehensive pulmonary rehabilitation. The subjects were eight patients with COPD with obstructive ventilation disorder as severe as 31.5 +/- 6% of FEV 1.0%. Pulmonary physical therapy was performed for eight weeks in a group administered one bottle of dietary supplement with a high Fisher ratio abundant in branched chain amino acids once daily (200 kCal/ 200 mL, Fisher ratio 40), and in another group without administration. Before and after the physical therapy, six-minute waking examination, QOL assessment (using CRQ), serum protein and serum Fisher ratio were comparatively examined between the two groups. After the eight weeks of pulmonary physical therapy, serum Fisher ratios were evidently reduced and serum protein measurements were also decreased in the group without dietary supplement abundant in branched chain amino acids. Accordingly, more amino acid is needed due to enhanced consumption of muscular protein during pulmonary physical therapy, during which nutrient ingestion including a sufficient amount of branched amino acid is necessary. It is an important element in continuing comprehensive pulmonary rehabilitation for a longer period.

Usefulness of QVAR for the treatment of bronchial asthma--with and without use of an inhalation device.

The treatment of bronchial asthma with QVAR (hydrofluoroalkane-134a BDP; 3M Pharmaceuticals, St. Paul, MN, USA) is usually conducted without an inhalation assistance device. However, Japanese patients who experience difficulty in coordinating activation with inspiration of inhaled steroid drugs are instructed on the use of such a device. We therefore examined the necessity of using an inhalation assistance device (INSPIR-EASE, IE) and its effect on quality of life (QOL) in the treatment of patients with bronchial asthma taking QVAR. Hence, lung function and QOL associated with taking QVAR plus IE or QVAR alone were examined by a cross-over method in 44 bronchial asthma patients (STEP 2 or 3) over 20 years of age. In all patients, lung function tests conducted 12 weeks after start of treatment indicated significant improvements of forced expiratory volume in 1 second (FEV1) with QVAR alone compared with QVAR plus IE (p < 0.05). In patients less than 70 years of age, significant improvements of forced vital capacity (FVC) and nitric oxide (NO) were also observed with QVAR alone compared with QVAR plus IE (p < 0.05). Examination of QOL the Living with Asthma Questionnaire indicated that medication usage was significantly improved with QVAR alone compared with QVAR plus IE. Significant improvement of FEV1 was observed with QVAR alone compared with QVAR plus IE, and additionally in patients less than 70 years of age improvement of FVC and NO was also marked. This study confirmed the usefulness of QVAR alone in patients with bronchial asthma.

[A case of acute pulmonary thromboembolism accompanied by anomalous inferior vena cava with azygous continuation].

A 38-year-old man with atopic dermatitis presented with right chest pain and dyspnea. Previously, he had received 2mg of betamethasone daily, to prevent rejection of the right transplanted cornea, for 24 days. His body temperature was 37.4 degrees C, peripheral leucocyte count measured 12,000/mm3, and C-reactive protein was 6.3 mg/dl. A computed tomogram of the chest revealed infiltration in the right lower lung field, and he was then treated for pneumonia. The second day he fell down one flight of stairs due to a syncopal attack and received a head injury. At this point his vital blood pressure was 102/55 mmHg, heart rate was 130/min and SpO2 under breathing room air was 76%. These findings indicated possible acute pulmonary thromboembolism. Enhanced computed tomography revealed pulmonary arteries occluded by massive thrombosis and anomalous inferior vena cava with azygous continuation. To decrease the risk of further cerebral bleeding, anti-coagulation therapy was administered with only 24,000 IU/day of heparin. Following treatment, the patient completely recovered. We reported this rare case of acute pulmonary thromboembolism accompanied by anomalous inferior vena cava with azygous continuation.

Role of muscarinic acetylcholine receptors in a guinea pig model of asthma.

We examined the density of muscarinic acetylcholine receptor (mACh-R) subtypes (M1R, M2R and M3R) in guinea pig lung. The density of M3R in the lung tissue of ovalbumin (OA)-sensitized guinea pigs was higher than that in the control group. However, no difference was observed in the affinity of M3R between the sensitized and the control lungs. No difference was observed in the density and affinity of M1R and M2R in sensitized and control lungs. Pilocarpine, which is an M2R stimulant, increased the density of M3R in the lung tissue and the rate of the increase in sensitized guinea pigs was less than that in the control group. In contrast, methoctranine, which is an M2R antagonist, decreased the density of M3R and the rate ofthis decrease was the same in the sensitized and control groups. These results suggest that, in OA-sensitized guinea pigs, a dysfunction of M2R leads to the abnormal density of M3R.